Islets are usually infused into the patient's liver,. The patient's body, however, will treat the infused islets just as it would any other introduction of foreign tissue: the immune system will attack the islets as it would a viral infection, leading to the risk of transplant rejection. Thus, the patient needs to undergo treatment involving immunosuppressants, which reduce immune system activity. Recent studies have shown that islet transplantation has progressed to the point that 58% of the patients in one study were insulin independent one year after the operation.
In the period from 1999 to 2004, 471 patients with type 1 diabetes have received islet transplants at 43 institutions worldwide.
Researchers use a mixture of highly purified enzymes (Collagenase) to isolate islets from the pancreas of a deceased donor. Collagenase solution is injected into the pancreatic duct which runs through the head, body and tail of the pancreas. Delivered this way, the enzyme solution causes distension of the pancreas, which is subsequently cut into small chunks and transferred into so-called Ricordi's chamber, where digestion takes place until the islets are liberated and removed from the solution. Isolated islets are then separated from the exocrine tissue and debris in a process called purification.
During the transplant, a radiologist uses ultrasound and radiography to guide placement of a catheter through the upper abdomen and into the portal vein of the liver. The islets are then infused through the catheter into the liver. The patient will receive a local anesthetic. If a patient cannot tolerate local anesthesia, the surgeon may use general anesthesia and do the transplant through a small incision. Possible risks of the procedure include bleeding or blood clots.
It takes time for the islets to attach to new blood vessels and begin releasing insulin. The doctor will order many tests to check blood glucose levels after the transplant, and insulin may be needed until control is achieved.
Seen another way, patients with heart, liver, lung, or kidney failure have a dismal prognosis for survival, so the toxicity associated with immunosuppression is warranted (the benefits of graft survival outweigh the risks associated with the medications). But for the subset of patients with diabetes and preserved kidney function, even those with long-standing and difficult-to-control disease, the prognosis for survival is comparatively much better. In addition to the immunosuppressive toxicities, other risks are associated with the islet transplant procedure itself, including intra-abdominal hemorrhage following the transplant, and portal vein thrombosis. The fact that there is already a good alternative to islet transplantation (i.e. the modern intensive insulin regimen) forces us to regard any newer, riskier interventions with a critical eye.
Like all transplantation therapies, islet transplantation is also handicapped by the limited donor pool. The numbers are striking; at least 1 million Americans have type 1 diabetes mellitus, and only a few thousand donor pancreata are available each year. To circumvent this organ shortage problem, researchers continue to look for ways to "grow" islets—or at least cells capable of physiologically regulated insulin secretion—in vitro, but currently only islets from cadaveric donors can be used to restore euglycemia. Further exacerbating the problem (and unlike kidney, liver, and heart transplants, where only one donor is needed for each recipient) most islet transplant patients require islets from two or more donors to achieve euglycemia. Lastly, the current methods for islet isolation need improvement, since only about half of attempted isolations produce transplant-ready islets.
While islet transplantation research has made important progress and the success stories are encouraging, the long-term safety and efficacy of the procedure remain unclear. Other concerns relating to the field include questions about the impact of having insulin-producing foreign cells within the hepatic parenchyma, the long-term consequences of elevated portal pressures resulting from the islet infusion, and the fact that islet recipients can be sensitized against donor tissue types, making it more difficult to find a suitable donor should another life-saving transplant be required in the future. Also, very few islet transplant recipients have remained euglycemic without the use of any exogenous insulin beyond four years post-transplant. Thus, while most islet recipients achieve better glycemia control and suffer less serious hypoglycemia, islet transplantation continues to fall short of the definitive diabetes cure.
Islet cell transplant's "perfect storm" results in new legislation, CMS reg, $75 million in research funding.(Pancreatic Islet Cell Transplantation Act of 2004)(Centers for Medicare and Medicaid Services)
Oct 15, 2004; It's islet cell transplantation's "perfect storm." In the last 7 months, pancreatic islet cell transplantation has been swept to...
Increased parathyroid hormone-related peptide in patients with hypercalcemia associated with islet cell carcinoma
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From Lab to Clinic: Jdrf-Funded Researchers Launch Study of New Drug's Ability to Improve Islet Cell Transplants --First Patient Treatment Begins to Test Whether the Drug Emricasan, a Pan-Caspase Inhibitor, Could Improve and Maintain Insulin Independence in Islet Cell Transplantation Patients with Type 1 Diabetes
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